Generic placeholder image

Current Neurovascular Research

Editor-in-Chief

ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

Review Article (Mini-Review)

Neurological Complications in COVID-19 Patients and its Implications for Associated Mortality

Author(s): Hanin A. AboTaleb*

Volume 17 , Issue 4 , 2020

Page: [522 - 530] Pages: 9

DOI: 10.2174/1567202617666200727124704

Price: $65

Abstract

Coronavirus is an enveloped, non-segmented, positive-polarity and single-stranded RNA virus. It has four types of genera that infect mammals and birds, with only alpha and beta types found to affect humans with varying severity. A specific clade of beta coronaviruses is reported as lethal zoonotic viruses and has created major epidemic troubles, starting with the severe acute respiratory syndrome (SARS) in 2002, then the Middle East respiratory syndrome (MERS) in 2012, and lastly Coronavirus Disease 2019 (COVID-19) in 2019. However, many neurological complications reported in COVID-19 patients have highlighted a critical pattern of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Awareness of such an association could create new insight to consider neurological manifestations as a COVID-19 differential diagnosis during the pandemic period of COVID-19 to avoid delayed diagnosis and prevent further transmission.

This mini-review aims to collect the current knowledge regarding the mechanism behind the neuroinvasive capacity of SARS-CoV-2, to summarize the common documented neurological symptoms and associated complications in COVID-19 patients, and to review the impact of neurological manifestations on COVID-19 mortality.

Keywords: COVID-19, coronavirus, neurology, headache, single-stranded RNA virus, neurological diseases.

[1]
McGavern DB, Kang SS. Illuminating viral infections in the nervous system. Nat Rev Immunol 2011; 11(5): 318-29.
[http://dx.doi.org/10.1038/nri2971] [PMID: 21508982]
[2]
Desforges M, Le Coupanec A, Brison E, Meessen-Pinard M, Talbot PJ. Neuroinvasive and neurotropic human respiratory coronaviruses: potential neurovirulent agents in humans. Adv Exp Med Biol 2014; 807: 75-96.
[http://dx.doi.org/10.1007/978-81-322-1777-0_6] [PMID: 24619619]
[3]
Levinson W. Review of medical microbiology and immunology. 15th ed. McGraw-Hill Medical: USA, 2017.
[4]
Ng Kee Kwong KC, Mehta PR, Shukla G, Mehta AR. COVID-19, SARS and MERS: A neurological perspective. J Clin Neurosci, 2020; [Epub ahead of print].
[5]
Totura AL, Bavari S. Broad-spectrum coronavirus antiviral drug discovery. Expert Opin Drug Discov 2019; 14(4): 397-412.
[http://dx.doi.org/10.1080/17460441.2019.1581171] [PMID: 30849247]
[6]
Li Y-C, Bai W-Z, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol 2020; 92(6): 552-5.
[http://dx.doi.org/10.1002/jmv.25728] [PMID: 32104915]
[7]
(Covid-19) Disease interactive dashboard Saudi Center for Disease Prevention and Control 2020. Available from: https://covid19.cdc.gov.sa/ar/daily-updates-ar/
[8]
Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med 2020; 46(5): 846-8.
[http://dx.doi.org/10.1007/s00134-020-05991-x] [PMID: 32125452]
[9]
Vincent J-L, Taccone FS. Understanding pathways to death in patients with COVID-19. Lancet Respir Med 2020; 8(5): 430-2.
[http://dx.doi.org/10.1016/S2213-2600(20)30165-X] [PMID: 32272081]
[10]
Xu Z, Shi L, Wang Y, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 2020; 8(4): 420-2.
[http://dx.doi.org/10.1016/S2213-2600(20)30076-X] [PMID: 32085846]
[11]
Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020; 395(10229): 1054-62.
[http://dx.doi.org/10.1016/S0140-6736(20)30566-3] [PMID: 32171076]
[12]
Du R-H, Liang L-R, Yang C-Q, et al. Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: A prospective cohort study. Eur Respir J 2020; 55(5): 2000524.
[http://dx.doi.org/10.1183/13993003.00524-2020] [PMID: 32269088]
[13]
Onder G, Rezza G, Brusaferro S. Case-Fatality rate and characteristics of patients dying in relation to COVID-19 in Italy. JAMA 2020; 323(18): 1775-6.
[http://dx.doi.org/10.1001/jama.2020.4683] [PMID: 32203977]
[14]
Bohmwald K, Galvez NMS, Rios M, Kalergis AM. Neurologic alterations due to respiratory virus infections. Front Cell Neurosci 2018; 12: 386.
[http://dx.doi.org/10.3389/fncel.2018.00386] [PMID: 30416428]
[15]
Asadi-Pooya AA, Simani L. Central nervous system manifestations of COVID-19: A systematic review. J Neurol Sci 2020; 413116832
[http://dx.doi.org/10.1016/j.jns.2020.116832] [PMID: 32299017]
[16]
Burks JS, DeVald BL, Jankovsky LD, Gerdes JC. Two coronaviruses isolated from central nervous system tissue of two multiple sclerosis patients. Science 1980; 209(4459): 933-4.
[http://dx.doi.org/10.1126/science.7403860] [PMID: 7403860]
[17]
Murray RS, Brown B, Brian D, Cabirac GF. Detection of coronavirus RNA and antigen in multiple sclerosis brain. Ann Neurol 1992; 31(5): 525-33.
[http://dx.doi.org/10.1002/ana.410310511] [PMID: 1596089]
[18]
Stewart JN, Mounir S, Talbot PJ. Human coronavirus gene expression in the brains of multiple sclerosis patients. Virology 1992; 191(1): 502-5.
[http://dx.doi.org/10.1016/0042-6822(92)90220-J] [PMID: 1413524]
[19]
Arbour N, Day R, Newcombe J, Talbot PJ. Neuroinvasion by human respiratory coronaviruses. J Virol 2000; 74(19): 8913-21.
[http://dx.doi.org/10.1128/JVI.74.19.8913-8921.2000] [PMID: 10982334]
[20]
Hung EC, Chim SS, Chan PK, et al. Detection of SARS coronavirus RNA in the cerebrospinal fluid of a patient with severe acute respiratory syndrome. Clin Chem 2003; 49(12): 2108-9.
[http://dx.doi.org/10.1373/clinchem.2003.025437] [PMID: 14633896]
[21]
Lau K-K, Yu W-C, Chu C-M, Lau S-T, Sheng B, Yuen K-Y. Possible central nervous system infection by SARS coronavirus. Emerg Infect Dis 2004; 10(2): 342-4.
[http://dx.doi.org/10.3201/eid1002.030638] [PMID: 15030709]
[22]
Saad M, Omrani AS, Baig K, et al. Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: A single-center experience in Saudi Arabia. Int J Infect Dis 2014; 29: 301-6.
[http://dx.doi.org/10.1016/j.ijid.2014.09.003] [PMID: 25303830]
[23]
Baig AM. Neurological manifestations in COVID-19 caused by SARS-CoV-2. CNS Neurosci Ther 2020; 26(5): 499-501.
[http://dx.doi.org/10.1111/cns.13372] [PMID: 32266761]
[24]
Mao L, Wang M, Chen S, He Q, Chang J, Hong C, et al. Neurological manifestations of hospitalized patients with COVID-19 in Wuhan, China: A retrospective case series study MedRxiv 2020.
[25]
Sohal S, Mossammat M. COVID-19 presenting with seizures. IDCases 2020; 20: e00782.
[http://dx.doi.org/10.1016/j.idcr.2020.e00782] [PMID: 32363146]
[26]
Glass WG, Subbarao K, Murphy B, Murphy PM. Mechanisms of host defense following severe acute respiratory syndrome-coronavirus (SARS-CoV) pulmonary infection of mice. J Immunol 2004; 173(6): 4030-9.
[http://dx.doi.org/10.4049/jimmunol.173.6.4030] [PMID: 15356152]
[27]
Li K, Wohlford-Lenane C, Perlman S, et al. Middle East respiratory syndrome coronavirus causes multiple organ damage and lethal disease in mice transgenic for human dipeptidyl peptidase 4. J Infect Dis 2016; 213(5): 712-22.
[http://dx.doi.org/10.1093/infdis/jiv499] [PMID: 26486634]
[28]
Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181(2): 271-280.e8.
[http://dx.doi.org/10.1016/j.cell.2020.02.052] [PMID: 32142651]
[29]
Xia H, Lazartigues E. Angiotensin-converting enzyme 2 in the brain: Properties and future directions. J Neurochem 2008; 107(6): 1482-94.
[http://dx.doi.org/10.1111/j.1471-4159.2008.05723.x] [PMID: 19014390]
[30]
Chen R, Wang K, Yu J, Chen Z, Wen C, Xu Z. The spatial and cell-type distribution of SARS-CoV-2 receptor ACE2 in human and mouse brain. bioRxiv 2020; 2020: PPR149891. 00.
[http://dx.doi.org/10.1101/2020.04.07.030650]
[31]
Sepehrinezhad A, Shahbazi A, Negah SS. COVID-19 virus may have neuroinvasive potential and cause neurological complications: A perspective review. J Neurovirol 2020; 26(3): 324-9.
[http://dx.doi.org/10.1007/s13365-020-00851-2] [PMID: 32418055]
[32]
Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol 2008; 82(15): 7264-75.
[http://dx.doi.org/10.1128/JVI.00737-08] [PMID: 18495771]
[33]
McCray PB Jr, Pewe L, Wohlford-Lenane C, et al. Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus. J Virol 2007; 81(2): 813-21.
[http://dx.doi.org/10.1128/JVI.02012-06] [PMID: 17079315]
[34]
Li YC, Bai WZ, Hirano N, et al. Neurotropic virus tracing suggests a membranous-coating-mediated mechanism for transsynaptic communication. J Comp Neurol 2013; 521(1): 203-12.
[http://dx.doi.org/10.1002/cne.23171] [PMID: 22700307]
[35]
Filatov A, Sharma P, Hindi F, Espinosa PS. Neurological Complications of Coronavirus Disease (COVID-19): Encephalopathy. Cureus 2020; 12(3): e7352-52.
[http://dx.doi.org/10.7759/cureus.7352] [PMID: 32328364]
[36]
Haddad S, Tayyar R, Risch L, et al. Encephalopathy and seizure activity in a COVID-19 well controlled HIV patient. IDCases 2020; 21: e00814-14.
[http://dx.doi.org/10.1016/j.idcr.2020.e00814] [PMID: 32426230]
[37]
Ye M, Ren Y, Lv T. Encephalitis as a clinical manifestation of COVID-19. Brain Behav Immun, 2020; [Epub ahead of print].
[38]
Varatharaj A, Thomas N, Ellul M, et al. UK-wide surveillance of neurological and neuropsychiatric complications of COVID-19: The first 153 patients. SSRN J 2020. Available from: https://ssrn.com/abstract=3601761
[39]
Ellul M, Benjamin L, Singh B, et al. Neurological associations of COVID-19 SSRN Electron J 2020.Availble from: https://ssrn.com/abstract=3589350
[40]
Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. COVID-19 associated acute hemorrhagic necrotizing encephalopathy: CT and MRI features. Radiology 2020; 201187201187
[http://dx.doi.org/10.1148/radiol.2020201187] [PMID: 32228363]
[41]
Zhou L, Zhang M, Wang J, Gao J. Sars-Cov-2: Underestimated damage to nervous system. Travel Med Infect Dis 2020; 101642: 101642.
[http://dx.doi.org/10.1016/j.tmaid.2020.101642] [PMID: 32220634]
[42]
Camdessanche JP, Morel J, Pozzetto B, Paul S, Tholance Y, Botelho-Nevers E. COVID-19 may induce Guillain-Barr?? syndrome. Rev Neurol (Paris) 2020; 176(6): 516-8.
[http://dx.doi.org/10.1016/j.neurol.2020.04.003] [PMID: 32334841]
[43]
Zhao H, Shen D, Zhou H, Liu J, Chen S. Guillain-Barr?? syndrome associated with SARS-CoV-2 infection: causality or coincidence? Lancet Neurol 2020; 19(5): 383-4.
[http://dx.doi.org/10.1016/S1474-4422(20)30109-5] [PMID: 32246917]
[44]
Deliwala S, Abdulhamid S, Abusalih MF, Al-Qasmi MM, Bachuwa G. Encephalopathy as the sentinel sign of a cortical stroke in a patient infected with Coronavirus Disease-19 (COVID-19). Cureus 2020; 12(5): e8121-21.
[http://dx.doi.org/10.7759/cureus.8121] [PMID: 32426200]
[45]
Oxley TJ, Mocco J, Majidi S, et al. Large-vessel stroke as a presenting feature of Covid-19 in the young. N Engl J Med 2020; 382(20): e60.
[http://dx.doi.org/10.1056/NEJMc2009787] [PMID: 32343504]
[46]
Fara MG, Stein LK, Skliut M, Morgello S, Fifi JT, Dhamoon MS. Macrothrombosis and stroke in patients with mild Covid-19 infection. J Thromb Haemost 2020; [Epub ahead of print].
[http://dx.doi.org/10.1111/jth.14938] [PMID: 32464707]
[47]
Zhao J, Rudd A, Liu R. Challenges and potential solutions of stroke care during the coronavirus disease 2019 (COVID-19) outbreak. Stroke 2020; 51(5): 1356-7.
[http://dx.doi.org/10.1161/STROKEAHA.120.029701] [PMID: 32228369]
[48]
Tunc A, Unlubas Y, Alemdar M, Akyuz E. Coexistence of COVID-19 and acute ischemic stroke report of four cases. J Clin Neurosci 2020; 77: 227-9.
[http://dx.doi.org/10.1016/j.jocn.2020.05.018] [PMID: 32409210]
[49]
Co COC, Yu JRT, Laxamana LC, David-Ona DIA. Intravenous Thrombolysis for Stroke in a COVID-19 Positive Filipino Patient, a Case Report. J Clin Neurosci 2020; 77: 234-6.
[http://dx.doi.org/10.1016/j.jocn.2020.05.006] [PMID: 32414622]
[50]
Alberti P, Beretta S, Piatti M, et al. Guillain-Barre syndrome related to COVID-19 infection. Neurol Neuroimmunol Neuroinflamm 2020; 7(4): e741.
[http://dx.doi.org/10.1212/NXI.0000000000000741] [PMID: 32350026]
[51]
Coen M, Jeanson G, Culebras Almeida LA, et al. Guillain-Barre syndrome as a complication of SARS-CoV-2 infection. Brain Behav Immun 2020; 87: 111-2.
[http://dx.doi.org/10.1016/j.bbi.2020.04.074] [PMID: 32360440]
[52]
El Otmani H, El Moutawakil B, Rafai MA, et al. Covid-19 and Guillain-Barr?? syndrome: More than a coincidence! Rev Neurol (Paris) 2020; 176(6): 518-9.
[http://dx.doi.org/10.1016/j.neurol.2020.04.007] [PMID: 32359804]
[53]
Ottaviani D, Boso F, Tranquillini E, et al. Early Guillain-Barre syndrome in coronavirus disease 2019 (COVID-19): A case report from an Italian COVID-hospital. Neurol Sci 2020; 41(6): 1351-4.
[http://dx.doi.org/10.1007/s10072-020-04449-8] [PMID: 32399950]
[54]
Virani A, Rabold E, Hanson T, et al. Guillain-Barre Syndrome associated with SARS-CoV-2 infection. IDCases 2020; 20: e00771.
[http://dx.doi.org/10.1016/j.idcr.2020.e00771] [PMID: 32313807]
[55]
Marta-Enguita J, Rubio-Baines I, Gaston-Zubimendi I. Fatal Guillain-Barre syndrome after infection with SARS-CoV-2. Neurologia 2020; 35(4): 265-7.
[http://dx.doi.org/10.1016/j.nrl.2020.04.004] [PMID: 32364124]
[56]
Padroni M, Mastrangelo V, Asioli GM, et al. Guillain-Barr?? syndrome following COVID-19: New infection, old complication? J Neurol 2020; 267(7): 1877-9.
[http://dx.doi.org/10.1007/s00415-020-09849-6] [PMID: 32333166]
[57]
Zhao K, Huang J, Dai D, Feng Y, Liu L, Nie S. Acute myelitis after SARS-CoV-2 infection: A case report MedRxiv 2020; [Epub ahead of print].
[58]
Zanin L, Saraceno G, Panciani PP, et al. SARS-CoV-2 can induce brain and spine demyelinating lesions. Acta Neurochir (Wien) 2020; 162(7): 1491-4.
[http://dx.doi.org/10.1007/s00701-020-04374-x] [PMID: 32367205]
[59]
Parsons T, Banks S, Bae C, Gelber J, Alahmadi H, Tichauer M. COVID-19-associated acute disseminated encephalomyelitis (ADEM). J Neurol 2020; [Epub ahead of print].
[http://dx.doi.org/10.1007/s00415-020-09951-9] [PMID: 32474657]
[60]
Zhang T, Rodricks MB, Hirsh E. COVID-19-Associated Acute Disseminated Encephalomyelitis: A Case Report MedRxiv 2020.
[61]
Abdelnour L, Eltahir Abdalla M, Babiker S. COVID 19 infection presenting as motor peripheral neuropathy. J Formos Med Assoc 2020; 119(6): 1119-20.
[http://dx.doi.org/10.1016/j.jfma.2020.04.024] [PMID: 32354690]
[62]
Bernard-Valnet R, Pizzarotti B, Anichini A, et al. Two patients with acute meningoencephalitis concomitant with SARS-CoV-2 infection. Eur J Neurol 2020; [Epub ahead of print].
[http://dx.doi.org/10.1111/ene.14298] [PMID: 32383343]
[63]
Duong L, Xu P, Liu A. Meningoencephalitis without respiratory failure in a young female patient with COVID-19 infection in Downtown Los Angeles, early April 2020. Brain Behav Immun 2020; 87: 33.
[http://dx.doi.org/10.1016/j.bbi.2020.04.024] [PMID: 32305574]
[64]
Moriguchi T, Harii N, Goto J, et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis 2020; 2020: 55-8.https://doi.org/https://doi.org/10.1016/j.ijid.2020.03.062
[65]
Wong PF, Craik S, Newman P, et al. Lessons of the month 1: A case of rhombencephalitis as a rare complication of acute COVID-19 infection. Clin Med (Lond) 2020; 20(3): 293-4.
[http://dx.doi.org/10.7861/clinmed.2020-0182] [PMID: 32371417]
[66]
Dinkin M, Gao V, Kahan J, et al. COVID-19 presenting with ophthalmoparesis from cranial nerve palsy. Neurology 2020; [Epub ahead of print].
[http://dx.doi.org/10.1212/WNL.0000000000009700] [PMID: 32358218]
[67]
Gutiérrez-Ortiz C, Méndez A, Rodrigo-Rey S, et al. Miller Fisher Syndrome and polyneuritis cranialis in COVID-19. Neurology 2020; [Epub ahead of print].
[http://dx.doi.org/10.1212/WNL.0000000000009619] [PMID: 32303650]
[68]
Escalada PS, Garriga F-BL. Paciente con clínica neurológica como única manifestación de infección por SARS-CoV-2. Neurología 2020; 35(4): 271-72.https://doi.org/https://doi.org/10.1016/j.nrl.2020.04.010
[69]
Dixon L, Varley J, Gontsarova A, et al. COVID-19-related acute necrotizing encephalopathy with brain stem involvement in a patient with aplastic anemia. Neurol Neuroimmunol Neuroinflamm 2020; 7(5): e789.
[http://dx.doi.org/10.1212/NXI.0000000000000789] [PMID: 32457227]
[70]
Paniz-Mondolfi A, Bryce C, Grimes Z, et al. Central nervous system involvement by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). J Med Virol 2020; 92(7): 699-702.
[http://dx.doi.org/10.1002/jmv.25915] [PMID: 32314810]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy